The research effort in the lab revolves around questions involving the expression and function of protein tyrosine phosphatases (PTPases) in the regulation of signaling, the cell cycle and transformation. The systems under study are differentiation and activation of T and B lymphocytes, and the transformation of breast epithelial cells by oncogenic tyrosine kinases.
The aim i s to study the expression and functional role of LAR and CD45 PTPases in breast cells and lymphoid cells. LAR and CD45 are receptor-like transmembrane proteins containing complex glycosylated external domains and very large cytoplasmic domains containing 2 PTPase modules. The external domains undergo alternative exon splicing which has been extensively studied in our laboratory by use of reverse transcription PCR. Currently we are investigating the role of phosphorylation of the cytoplasmic domain in the regulation of PTPase activity. In addition, the modulation of CD45 PTPase activity has been studied through the cell cycle of B and T lymphocytes. CD45 PTPase activity was found to be elevated in late mitosis and in cytokinesis. The detailed phosphorylation of LAR and CD45 in activated cells and in cell cycle phases will be determined by phosphoamino acid analysis, by phosphopeptide mapping and by MALDI-MS. Mass spectrometry is essential to the identification of regulatory phosphorylation sites in the small amounts of the PTPases that can be obtained from cells in signaling experiments. Ultimately, the understanding of phosphorylation and dephosphorylation of signaling molecules should lead to strategies for the control of unchecked proliferation characteristic of cancer.
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